Bioinformatics analysis and quantitative weight of evidence assessment to map the potential mode of actions of bisphenol A. (15th March 2021)

• Record Type: Journal Article
• Authors: Li, Xiaomeng; Ni, Mengmei; Yang, Zhirui; Chen, Xuxi; Zhang, Lishi; Chen, Jinyao
• Is Part Of: Environmental pollution. Volume 273(2021)
• Publication Date: 2021-03-15
• Subjects: Bioinformatics analysis -- Quantitative weight of evidence -- Mode of action -- Bisphenol A; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.116469
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Bisphenol A (BPA) is a classical chemical contaminant in food, and the mode of action (MOA) of BPA remains unclear, constraining the progress of risk assessment. This study aims to assess the potential MOAs of BPA regarding reproductive/developmental toxicity, neurological toxicity, and proliferative effects on the mammary gland and the prostate potentially related to carcinogenesis by using the Comparative Toxicogenomics Database (CTD)-based bioinformatics analysis and the quantitative weight of evidence (QWOE) approach on the basis of the principles of Toxicity Testing in the 21st Century . The CTD-based bioinformatics analysis results showed that estrogen receptor 1, estrogen receptor 2, mitogen-activated protein kinase (MAPK) 1, MAPK3, BCL2 apoptosis regulator, caspase 3, BAX, androgen receptor, and AKT serine/threonine kinase 1 could be the common target genes, and the apoptotic process, cell proliferation, testosterone biosynthetic process, and estrogen biosynthetic process might be the shared phenotypes for different target organs. In addition, the KEGG pathways of the BPA-induced action might involve the estrogen signaling pathway and pathways in cancer. After the QWOE evaluation, two potential estrogen receptor-related MOAs of BPA-induced testis dysfunction and learning-memory deficit were proposed. However, the confidence and the human relevance of the two MOAs were moderate, prompting studies to improve the MOA-based risk assessment of BPA. Graphical abstract: Image 1 Highlights: ESR1, ESR2, MAPK1, and MAPK3 can be the common target genes. The KEGG pathways of the BPA-induced action involves the estrogen signaling pathway. The potential of the ER-related MOA of BPA-induced testis dysfunction is proposed. The potential of the ER-related MOA of BPA-induced learning-memory deficit is proposed.